Role of long non-coding RNA in tumor drug resistance

Chemotherapy has been extensively used in tumor treatment, including either systemic or local treatment. Miserably, in many kinds of cancers, chemotherapy is gradually insensitive. The mechanisms of tumor drug resistance have been widely explored, yet have not been fully characterized. With several studies in the development of drug resistance, recent works have highlighted the involvement of non-coding RNAs in tumor development. A growing number of long non-coding RNAs (lncRNAs) have been identified as transcripts of larger than 200 nucleotides in length, which have low coding potential, but potentially coding small peptides with 50-70 amino acids. Despite so often being branded as transcriptional noise, it is becoming increasingly clear that a large number of lncRNAs are crucial molecular regulators of the processes of tumor involving the initiation and progression of human tumor. More recently, accumulating evidence is revealing an important role of lncRNA in tumor drug resistance and lncRNA expression profiling can be correlated with the evolution of tumor drug resistance. The long non-coding-RNA-mediated form of drug resistance brings yet another mechanism of drug resistance. So, exploiting the newly emerging knowledge of lncRNAs for the development of new therapeutic applications to overcome human tumor drug resistance will be significant.

lncRNAs may induce tumor drug resistance by promoting the substrate efflux function (black arrows) of the multidrug-resistant transporter P-glycoprotein (P-gp) and the breast cancer resistance protein (BCRP) . In addition, it has been proposed that lncRNAs may affect multiple pathways to produce drug resistance in tumor cells. Blue lines represent downregulation or demotion; orange lines represent upregulation or promotion. Hexagon nodes represent lncRNAs that regulate target gene, RNA, and protein to contribute to drug resistance through either different or the same ways.